Hypoxia Effects on <i>Trypanosoma cruzi</i> Epimastigotes Proliferation, Differentiation, and Energy Metabolism
Francis M. S. Saraiva,
Daniela Cosentino-Gomes,
Job D. F. Inacio,
Elmo E. Almeida-Amaral,
Orlando Louzada-Neto,
Ana Rossini,
Natália P. Nogueira,
José R. Meyer-Fernandes,
Marcia C. Paes
Affiliations
Francis M. S. Saraiva
Trypanosomatids and Vectors Interaction Laboratory, Department of Biochemistry, Roberto Alcantara Gomes Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro 20550-013, Brazil
Daniela Cosentino-Gomes
Institute of Medical Biochemistry Leopoldo De Meis, Center for Health Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941-901, Brazil
Job D. F. Inacio
Tripanosomatide Biochemistry Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Manguinhos, Rio de Janeiro 21040-900, Brazil
Elmo E. Almeida-Amaral
Tripanosomatide Biochemistry Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Manguinhos, Rio de Janeiro 21040-900, Brazil
Orlando Louzada-Neto
Laboratory of Toxicology and Molecular Biology, Department of Biochemistry, IBRAG- UERJ, Rio de Janeiro 20511-010, Brazil
Ana Rossini
Laboratory of Toxicology and Molecular Biology, Department of Biochemistry, IBRAG- UERJ, Rio de Janeiro 20511-010, Brazil
Natália P. Nogueira
Trypanosomatids and Vectors Interaction Laboratory, Department of Biochemistry, Roberto Alcantara Gomes Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro 20550-013, Brazil
José R. Meyer-Fernandes
Institute of Medical Biochemistry Leopoldo De Meis, Center for Health Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941-901, Brazil
Marcia C. Paes
Trypanosomatids and Vectors Interaction Laboratory, Department of Biochemistry, Roberto Alcantara Gomes Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro 20550-013, Brazil
Trypanosoma cruzi, the causative agent of Chagas disease, faces changes in redox status and nutritional availability during its life cycle. However, the influence of oxygen fluctuation upon the biology of T. cruzi is unclear. The present work investigated the response of T. cruzi epimastigotes to hypoxia. The parasites showed an adaptation to the hypoxic condition, presenting an increase in proliferation and a reduction in metacyclogenesis. Additionally, parasites cultured in hypoxia produced more reactive oxygen species (ROS) compared to parasites cultured in normoxia. The analyses of the mitochondrial physiology demonstrated that hypoxic condition induced a decrease in both oxidative phosphorylation and mitochondrial membrane potential (ΔΨm) in epimastigotes. In spite of that, ATP levels of parasites cultivated in hypoxia increased. The hypoxic condition also increased the expression of the hexokinase and NADH fumarate reductase genes and reduced NAD(P)H, suggesting that this increase in ATP levels of hypoxia-challenged parasites was a consequence of increased glycolysis and fermentation pathways. Taken together, our results suggest that decreased oxygen levels trigger a shift in the bioenergetic metabolism of T. cruzi epimastigotes, favoring ROS production and fermentation to sustain ATP production, allowing the parasite to survive and proliferate in the insect vector.
